The Trimera mouse: a system for generating human monoclonal antibodies and modeling human diseases

A Trimera mouse is constructed through a three-step process. Firstly, a normal mouse host is rendered immuno-incompetent by a lethal split-dose total body irradiation. Secondly, the myeloid and erythroid lineages are reconstituted by transplantation of bone marrow cells from a genetically immune-deficient mouse donor. Thirdly. the resulting preconditioned mouse is transplanted with human cells or tissues that can be maintained in the foreign, yet supporting, environment for a considerable period of time. Immunization of Trimera mice, engrafted with human immune cells, induces a strong human immune response, thereby enabling generation of human therapeutic monoclonal antibodies (mAbs) via hybridoma technology. Transplantation of infected human tissue into the preconditioned mice results in the creation of Trimera mouse models for human diseases.